microscopic haematuria - who and when to refer haematuria.pdf · microscopic haematuria - who and...

Microscopic haematuria

- who and when to refer

Stephen Marks

Consultant Paediatric Nephrologist

Great Ormond Street Hospital for Children and

UCL Institute of Child Health, London, UK

Paediatric Nephrology for the General Paediatrician Manchester, Friday 24 June 2016

Introduction

• Case presentations

• Does haematuria matter ?

• Microscopic versus macroscopic haematuria

• Does management change with proteinuria ?

• Evidence-based medicine

• Conclusions

Case presentations

Case 1

• 6 year old girl

– developed viral URTI (sore throat and cough) 3w ago

– both parents and her younger sister also had URTI

– 48 hour history of vomiting, coca-cola urine

– 24 hour history of periorbital oedema, oliguria

– examination revealed

• hypovolaemia, peripheral oedema, SBP = 130mmHg

– investigations revealed

• PCr of 150mol/l, albumin 22g/l

• proteinuria 3+, haematuria 3+, red cell casts

Case 2

• 3 year old girl

– 6 month history of recurrent macroscopic haematuria

– associated with precipitant of viral URTI

– eating and drinking normally without vomiting

– no family or past medical history

– normal examination

– investigations revealed

• normal plasma creatinine and albumin

• no proteinuria, haematuria 3+, no casts

• no calculi on ultrasound

Case 3

• 12 year old boy

– admitted with 4 day history of severe left loin pain

– 3 week history of afebrile, recurrent episodes of macroscopic haematuria

– decreased oral intake

– examination revealed • severe left loin tenderness

– investigations revealed • normal plasma creatinine and albumin

• trace proteinuria, haematuria 4+, no casts

Case 3

• 12 year old boy

– admitted with 4 day history of severe left loin pain

– 3 week history of afebrile, recurrent episodes of macroscopic haematuria

– decreased oral intake

– examination revealed • severe left loin tenderness

– investigations revealed • normal plasma creatinine and albumin

• trace proteinuria, haematuria 4+, no casts

• 2mm left non-obstructing renal calculus on ultrasound

Does haematuria matter ?

Should we investigate ?

Macroscopic haematuria




YES




YES


NO

Epidemiology of haematuria


• Clear diagnosis

• 0.2% prevalence

• Resolution varies


• Definition varies

• 0.5-1.6% prevalence

• 70% resolution by 6m

Does haematuria matter ?

• Only if recurrent macroscopic haematuria

– always investigate if proteinuria present

• Exclude non-glomerular cause

• Exclude familial disorder

• Consider future of child

– eg. occupation, insurance

Renal biopsies for recurrent macro or

intermittent microscopic haematuria

27%

24%15%

15%

19%Alports

IgAN

TBM

Normal

Miscellaneous

n = 322 children

Urinalysis

• Convenient so widespread use

– Store in dry environment

– Automated results with printout

• Blood detected by peroxidase-like action and detects small quantities

– Negative result excludes haematuria

• Protein detected by tetrabromophenol

– Albumin demonstrates better binding


• May be asymptomatic – eg. family screening so consider BP, creatinine,

UA:UC, renal biopsy and observe +/- treat

• Child with symptoms and/or signs – eg. fever, lethargy, hypertension, oedema

• Child with urinary tract symptoms – eg. dysuria, urgency, frequency, enuresis

• Child with non-urinary tract symptoms – eg. rash, purpura, arthritis, jaundice, GI


• Fever, illness, trauma and extreme exertion may induce haematuria

• Where haematuria is related to a non-renal disease, it should disappear with resolution of primary disease

• If patient has microscopic haematuria – > demonstrate resolution

– > discharge if resolves or is intermittent over 6m with normal family dipstick, renal US, urine Ca:Cr

– > if associated with proteinuria or is persistent or is associated with complex disease or FHx then refer


without proteinuria

Cause Investigation

UTI MSSU M/C/S

Hypercalciuria Urine Ca:Cr

Renal calculi Renal US

Hydronephrosis Renal US

Renal biopsy for

microscopic haematuria

Pros Cons

Diagnosis Invasive procedure

Avoid later Ix

Genetic counselling No treatment

Reassurance - unless develops proteinuria

Follow-up

Population studies

160,000 Japanese

children annually

251 (0.2%) isolated


136 (54%) asymptomatic

microscopic haematuria 115 (46%) specific cause of


Isolated microscopic haematuria

(n = 251 children) • Asymptomatic isolated 136 54%

• Normal / menstruation 89 35%

• UTI (pyelonephritis / VUR 4) 14 6%

• Hypercalciuria (stone 1) 5 2%

• HSP nephritis (PMHx) 3 1.2%

• Hydronephrosis 2 0.8%

• PKD 1 0.4% – Hisano S et al (1991) Pediatr Nephrol 5:578-581

Prognosis of asymptomatic isolated


• Patients followed up for 7.4 (6-13) years

– Hypertension 0 0%

– Renal impairment 0 0%

– Proteinuria 1 0.8%

Visual examination of urine

• Macroscopic haematuria – may contain very small amounts of blood

• cf. MICROSCOPIC HAEMATURIA MAY CONTAIN SIGNIFICANT NUMBERS OF RBCs

– bright red blood staining may contain clots and indicates heavy bleeding

• eg. TRAUMA, COAGULOPATHY

• Cloudy urine – pyuria associated with UTI

• Gravel – associated with calcium, urate, cystine or struvite

Bloody urine - without blood

• Cause of red urine without haematuria – Foods

• eg. BEETROOT AND FOOD COLOURINGS

– Drugs • eg. RIFAMPICIN

– Haemoglobinuria

– Myoglobinuria

– Inborn errors of metabolism • eg. PORPHYRIA

– Urate crystals

– Factitious haematuria / MSBP

Bloody urine - without blood

• Cause of red urine without haematuria – Foods

• eg. BEETROOT AND FOOD COLOURINGS

– Drugs • eg. RIFAMPICIN

• eg. PORPHYRIA

– Urate crystals

– Factitious haematuria / MSBP

ALWAYS CONFIRM PRESENCE OF RED BLOOD

CELLS ON URINE MICROSCOPY


• Timing of haematuria – Renal cause

• if throughout micturition

– Bladder cause • terminal haematuria

• ?non-specific urethritis

– Urethral cause • at start of micturition

Causes of macroscopic haematuria

• Proven UTI 26%

• Suspected UTI 23%

• Perineal irritation 11%

• Trauma 6%

• Acute Nephritis 4%

• Coagulopathy 3%

• Stones 2%

• Tumour 1%

• Other 23% – Ingelfinger JR et al (1977) Pediatrics 59:557-561

Causes of macroscopic haematuria

• Exercise-induced

• Loin pain-haematuria syndrome

• Haemorrhagic cystitis

• Hypercalciuria

• Hyperuricosuria

• Bladder tumours / malakoplakia

– eg. rhabdomyosarcoma


without proteinuria

Cause Investigation

UTI MSSU M/C/S

Hypercalciuria Urine Ca:Cr

Renal calculi Renal US

Hydronephrosis Renal US

Papillary necrosis Renal US

RVT Doppler US

Others eg. Urethral/bladder abnormalities AV malformation, GN, SLE, IgA nephropathy, SCD, SBE

Management of

macroscopic haematuria

1. Confirm presence of RBCs on microscopy

2. History and physical examination (inc. BP)

3. MSSU -> treat if UTI

4. If non-confirmatory, family history and urinalysis with further investigations

• FBC, coagulation screen, ESR, CRP

• U&E’s, tCO2, albumin, ASOT, C3, C4, Ig’s. ANA

• Urine dipstick, culture, albumin, urate and calcium:creatinine

• Renal tract ultrasound +/- abdominal x-ray

5. Refer to paediatric nephrology • if renal impairment, proteinuria, hypertension etc

Developing proteinuria…

Proteinuria

• Clinical evaluation – macroscopic haematuria (menstruation)

– evidence of oedema and/or hypertension

• Bedside testing – concentrated sample

– orthostatic proteinuria (Early Morning Urine sample)

• Laboratory testing (including tubular vs glomerular) – nephrotic-range proteinuria (spot versus 24-hour collection)

• EMU ALBUMIN : CREATININE RATIO, SERUM ALBUMIN

– renal function

• PLASMA CREATININE AND ESTIMATED GFR

– percutaneous renal biopsy

Micro or macroscopic haematuria

with proteinuria

Cause Investigation

Glomerulonephritis FBC, U&E’s

C3, C4, ASOT

ANA, dsDNA

ANCA, Ig’s

Renal biopsy

Normal values (mg/mmol) for

urine albumin : creatinine ratios

Age UA:UC

0 - 1 w 3.0 - 44

1 w - 6 m 1.7 - 12.2

6 m - 2 y 1.5 - 8.7

2 - 5 y 0.5 - 3.3

5 - 10 y 0.2 - 4.5

10 - 16 y 0.1 - 7.4

Urine protein

Nephrotic range proteinuria and oedema

U&E, albumin, lipids

Consider referral if abnormal

features:

- age > 10 years

- evidence of systemic disease

- hypertension

- macroscopic haematuria

Rx prednisolone

2mg/kg/day (<60mg)

yes no

Repeat with first morning urine

UA : UC

normal

discharge

abnormal

Orthostatic

proteinuria?

Annual

follow-up

yes

no

Red blood cell cast

Treatment of proteinuria

• Immunosuppression for active GN

• ACE inhibitors and ARB treat hypertension and proteinuria – efferent arteriolar

dilatation reducing glomerular pressure

– commence

Rx enalapril 0.1mg/kg/d

– side-effects • ↑K and ↑PCr

• non-productive cough

• teratogen

Summary

• Microscopic haematuria – if continuous and confirmed RBC’s, check family

members and exclude proteinuria and hypertension

– discuss with family options of follow-up or biopsy

• Macroscopic haematuria – if recurrent and confirmed RBC’s, check timing during

urinary stream to help isolate cause

– investigations to exclude common conditions such as UTI and renal calculi

• Proteinuria – always investigate if persistent or non-orthostatic

– exclude nephrotic syndrome and glomerulonephritis

Any questions ?

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